Despite the increasing interest in this issue and the rapid increase in Japan, so far we are still not clear about the causes of this physiological degradation, let alone in-depth research. Now, the researchers use the currently popular technology? DNA chip (or DNA Microarray) to comprehensively analyze gene expression patterns, and made some progress. According to a report published in Science magazine (volume 287, page 2486) on March 31, 2000, a team led by Richard Lerner used chip technology to study the genetic changes of aging fibroblasts and found that certain changes can cause signs of aging- -The generation of wrinkles, at the same time, they also found some evidence that: damage to an organelle required for chromosome separation during cell division will cause gene instability and changes in gene function, which may be the cause of aging.
The researchers compared the gene expression differences between tissues of normal people of different ages and those with Hutchison-Gilford progeria (a disease that causes premature aging in children). Using fluorescently labeled DNA probes derived from reverse transcription of mRNA to hybridize with known genes on the DNA chip, 61 of the 6300 known genes were found to have expression changes with age. Most of the changes also occur in fibroblasts of patients with progeria. It indicates that there is indeed an accelerated aging process in these progeria patients who often die of heart disease in their teens.
There are some results that are not surprising. For example, there are several genes involved in the production of proteins that constitute the extracellular matrix that supports the skin and tissues, and their expression patterns change with age. The up-regulation of inflammation-related genes is also related to various geriatric diseases. However interesting is the down-regulation of the expression of 15 genes involved in controlling mitosis.
The down-regulation of mitotic-related genes usually leads to chromosome instability, which can lead to the loss of genes that inhibit tumor formation or activation of genes that promote tumor formation. The same chromosome instability may also be the cause of aging in a broad sense. Lerner's conclusion is: "ageing is predominantly a disease of mismanagement of cell division checkpoints" Although many studies have pointed out similar possibilities, Lerner provides strong evidence for this idea through the high energy screening of genes (microarray) . Another group has also used microarray technology to study the mechanism of aging (Science, 27, Aug, 1999, P13%). In the skeletal muscle of aging mice, 55 motility decreased or shut down, and many genes with decreased motility were related to energy production, protein and chemical synthesis, leading to muscle decline. On the contrary, some stress proteins related to the manipulation and repair of DNA proteins are activated.
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